In VitroActivity of Human-Simulated Epithelial Lining Fluid Exposures of Ceftaroline, Ceftriaxone, and Vancomycin against Methicillin-Susceptible and -Resistant Staphylococcus aureus

Abstract

ABSTRACTStaphylococcus aureus, including methicillin-susceptible (MSSA) and -resistant (MRSA) strains, is an important pathogen of bacterial pneumonia. As antibiotic concentrations at the site of infection are responsible for killing, we investigated the activity of human-simulated epithelial lining fluid (ELF) exposures of three antibiotics (ceftaroline, ceftriaxone, and vancomycin) commonly used for treatment ofS. aureuspneumonia. Anin vitropharmacodynamic model was used to simulate ELF exposures of vancomycin (1 g every 12 h [q12h]), ceftaroline (600 mg q12h and q8h), and ceftriaxone (2 g q24h and q12h). FourS. aureusisolates (2 MSSA and 2 MRSA) were evaluated over 72 h with a starting inoculum of ∼106CFU/ml. Time-kill curves were constructed, and microbiological response (change in log10CFU/ml from 0 h and the area under the bacterial killing and regrowth curve [AUBC]) was assessed in duplicate. The change in 72-h log10CFU/ml was largest for ceftaroline q8h (reductions of >3 log10CFU/ml against all strains). This regimen also achieved the lowest AUBC against all organisms (P< 0.05). Vancomycin produced reliable bacterial reductions of 0.9 to 3.3 log10CFU/ml, while the activity of ceftaroline q12h was more variable (reductions of 0.2 to 2.3 log10CFU/ml against 3 of 4 strains). Both regimens of ceftriaxone were poorly active against MSSA tested (0.1 reduction to a 1.8-log10CFU/ml increase). Against theseS. aureusisolates, ELF exposures of ceftaroline 600 mg q8h exhibited improved antibacterial activity compared with ceftaroline 600 mg q12h and vancomycin, and therefore, this q8h regimen deserves further evaluation for the treatment of bacterial pneumonia. These data also suggest that ceftriaxone should be avoided forS. aureuspneumonia.